Optimization of CV health helps to reduce ASCVD risk in individuals with elevated Lp(a)

In a MESA study analysis among subjects with no clinical ASCVD, optimal control of modifiable risk factors plus a healthy lifestyle was associated with a 55%–88% lower risk of incident ASCVD, regardless of Lp(a) levels.

This summary is based on the publication of Razavi AC, Reyes MP, Wilkins JT, et al. - Traditional Risk Factors, Optimal Cardiovascular Health, and Elevated Lipoprotein(a). Eur J Prev Cardiol. 2024 Nov 28:zwae382 [Online ahead of print]. doi: 10.1093/eurjpc/zwae382

Introduction and methods

Background

Lp(a), an LDL-like particle in which apo(a) is covalently bound to apoB-100, is a causal risk factor for ASCVD [1]. However, specific guidance on the primary prevention of ASCVD in individuals with elevated Lp(a) levels is lacking. In addition, the contribution of lifestyle to ASCVD risk in this population is not clear. To define CV health, the American Heart Association has introduced the Life’s Simple 7 (LS7) score, a simple and validated measure based on 7 risk factors (smoking, physical activity, BMI, diet, total cholesterol levels, blood pressure, and blood glucose levels) [2].

Aim of the study

The study aim was to assess the associations of traditional risk factor burden and the LS7 score with incident ASCVD in older adults with no clinical ASCVD at baseline, stratified by Lp(a) levels.

Methods

The MESA (Multi-Ethnic Study of Atherosclerosis) study is a prospective, longitudinal, population-based cohort study among 6814 individuals aged 45–84 years who were free of known clinical ASCVD at baseline (July 2000 to July 2002) and were enrolled at 6 US field centers [3]. Baseline Lp(a) measurements, data on risk factors, and follow-up for ASCVD events were available for 6676 participants. Median follow-up duration was 17.7 years. The LS7 score was categorized as follows: poor (score: 0–8), average (score: 9–10), and optimal (score: 11–14). Traditional factors included cigarette smoking, BMI, systolic and diastolic blood pressure, levels of fasting blood glucose, total cholesterol, HDL-c, and triglycerides, and eGFR.

Outcome

The main endpoint comprised incident ASCVD events, defined as definite or probable MI, resuscitated cardiac arrest, fatal CHD, fatal and nonfatal stroke, and other atherosclerotic or CV death.

Main results

• The rate of incident ASCVD events was higher in individuals with Lp(a) ≥50 mg/dL (n=1336; 20%) (10.1 events per 1000 person-years; 95%CI: 8.7–11.6) compared with subjects with Lp(a) 30–49 mg/dL (n=873; 13%) (8.4 events per 1000 person-years; 95%CI: 6.8–10.1) and those with <30 mg/dL (n=4467; 67%) (8.5 events per 1000 person-years; 95%CI: 7.8–9.1).
• Of the traditional risk factors, systolic blood pressure was associated with incident ASCVD in individuals with Lp(a) <30 mg/dL (HR per SD of 20 mmHg: 1.33; 95%CI: 1.17–1.51), whereas cigarette smoking (HR per SD of 18 pack years: 1.21; 95%CI: 1.08–1.36), BMI (HR per SD of 5 kg/m²: 1.20; 95%CI: 1.01–1.42), and fasting blood glucose levels (HR per SD of 26 mg/dL: 1.23; 95%CI: 1.11–1.37) showed associations with the incidence of ASCVD events in those with Lp(a) ≥50 mg/dL.
• For every LS7 score category, subjects with Lp(a) ≥50 mg/dL had a higher crude ASCVD event rate (per 1000 person-years) compared with those with Lp(a) 30–49 mg/dL or <30 mg/dL.
• There was no interaction between Lp(a) level and LS7 score for the risk of ASCVD events (P for interaction=0.60).
• Compared with a poor LS7 score, an optimal LS7 score conveyed a lower risk of incident ASCVD among participants with Lp(a) <30 mg/dL (HR: 0.45; 95%CI: 0.28–0.71; P<0.001), Lp(a) 30–49 mg/dL (HR: 0.12; 95%CI: 0.02–0.89; P=0.04), and Lp(a) ≥50 mg/dL (HR: 0.35; 95%CI: 0.13–0.99; P=0.04).

Conclusion

In this analysis of the MESA study among individuals with no clinical ASCVD, optimal control of modifiable risk factors plus a healthy lifestyle, summarized in an LS7 score, was associated with a 55%–88% lower risk of incident ASCVD, regardless of Lp(a) level. The authors’ conclusion is: “Our findings suggest that optimization of cardiovascular health can significantly reduce ASCVD risk in [individuals with elevated Lp(a) levels], [al]though residual risk remains.”

Find this article online at Eur J Prev Cardiol.

References

1. Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, Heffron SP, Kamstrup PR, et al. Lipoprotein(a): a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol 2022;42:e48–e60.
2. Ainsworth BE, Irwin ML, Addy CL, Whitt MC, Stolarczyk LM. Moderate physical activity patterns of minority women: the Cross-Cultural Activity Participation Study. J Womens Health Gend Based Med 1999;8:805–813.
3. Bild DE, Bluemke DA, Burke GL, Detrano R, Diez Roux AV, Folsom AR, et al. Multi-Ethnic Study of Atherosclerosis: objectives and design. Am J Epidemiol 2002; 156:871–881.